Arbaclofen placarbil: Development discontinued
Xenoport discontinued development of arbaclofen placarbil after top-line data from a 13-week, double-blind, U.S. Phase III trial in 228 patients with spasticity due to MS showed that the product missed the co-primary endpoints of improving physician-rated Maximum Ashworth Scale and 7-point PGIC scores from baseline to the end of the maintenance dose period vs. placebo. The most common adverse event reported was somnolence. Patients received placebo or twice-daily 15, 30 or 45 mg arbaclofen placarbil. The trial consisted of a 1-week placebo run-in period, 2 weeks of up-titration, 8 weeks at the maintenance dose and 2 weeks of down-titration.
On a call to investors to discuss the data, Xenoport said patients in the placebo arm had an "unexpectedly high" improvement of 0.94 units from baseline in Maximum Ashworth Scale score despite the use of a placebo run-in period. Additionally, the company said that inter-subject variability on the endpoint within treatment groups was "higher than expected." The company declined to disclose details. Xenoport, which had an SPA from FDA for the trial, previously said it had hoped the study would support the submission of an NDA under section 505(b)(2) of the Food, Drug and Cosmetic Act, which allows sponsors to reference data on safety and efficacy from the scientific literature or from previously approved products (see BioCentury, April 15). ...